The drug interaction potential of daprodustat when coadministered with pioglitazone, rosuvastatin, or trimethoprim in healthy subjects.

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Caltabiano S, Mahar KM, Lister K, Tenero D, Ravindranath R, Cizman B, Cobitz AR

The drug interaction potential of daprodustat when coadministered with pioglitazone, rosuvastatin, or trimethoprim in healthy subjects.

Pharmacol Res Perspect. 2018 Mar 9;6(2):e00327. doi: 10.1002/prp2.327. eCollection 2018 Apr.

PubMed ID

29545948 [ View in PubMed

]

Abstract

This study was conducted to evaluate the likelihood of daprodustat to act as a perpetrator in drug-drug interactions (DDI) with the CYP2C8 enzyme and OATP1B1 transporter using the probe substrates pioglitazone and rosuvastatin as potential victims, respectively. Additionally, this study assessed the effect of a weak CYP2C8 inhibitor, trimethoprim, as a perpetrator of a DDI with daprodustat. This was a two-part study: Part A assessed the effect of coadministration of daprodustat on the pharmacokinetics of pioglitazone and rosuvastatin in 20 subjects; Part B assessed the coadministration of trimethoprim on the pharmacokinetics of daprodustat in 20 subjects. Coadministration of 100 mg of daprodustat with pioglitazone or rosuvastatin had no effect on the plasma exposures of either probe substrate. When trimethoprim was coadministered with 25-mg daprodustat plasma daprodustat AUC and C(max) increased by 48% and 28%, respectively. Additionally, AUC and C(max) for the metabolite GSK2531401 were decreased by 32% and 40%, respectively. C(max) for the other metabolites was slightly decreased (~8-15%) but no changes in AUC were observed. As 100-mg daprodustat exceeds the planned top therapeutic dose, interaction potential of daprodustat as a perpetrator with substrates of the CYP2C8 enzyme and OATP1B1 transporters is very low. Conversely, daprodustat exposure (AUC and C(max)) is likely to increase moderately with coadministration of weak CYP2C8 inhibitors.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Daprodustat	Cytochrome P450 2C8	Protein	Humans	No	Substrate Inhibitor	Details

Drug Interactions

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drugs	Interaction
Integrate drug-drug interactions in your software
Daprodustat Ritonavir	The metabolism of Daprodustat can be decreased when combined with Ritonavir.
Daprodustat Erlotinib	The metabolism of Daprodustat can be decreased when combined with Erlotinib.
Daprodustat Fluticasone propionate	The metabolism of Daprodustat can be decreased when combined with Fluticasone propionate.
Daprodustat Clopidogrel	The metabolism of Daprodustat can be decreased when combined with Clopidogrel.
Daprodustat Candesartan cilexetil	The metabolism of Daprodustat can be decreased when combined with Candesartan cilexetil.